Differential Target Multiplexed Spinal Cord Stimulation: A UK Cost-Effectiveness Analysis.

OBJECTIVES: The aim of this economic analysis was to evaluate the cost-effectiveness of differential target multiplexed spinal cord stimulation (DTM-SCS) for treating chronic intractable low back pain, compared with conventional spinal cord stimulation (C-SCS) and conservative medical management (CMM), by updating and expanding the inputs for a previously published cross-industry model. MATERIALS AND METHODS: This model comprised a 12-month decision-tree phase followed by a long-term Markov model. Costs and outcomes were calculated from a UK National Health Service perspective, over a base-case horizon of 15 years and up to a maximum of 40 years. All model inputs were derived from published literature or other deidentified sources and updated to reflect recent clinical trials and costs. Deterministic and one-way sensitivity analyses were performed to calculate costs and quality-adjusted life-years (QALYs) across the 15-year time horizon and to explore the impact of individual parameter variability on the cost-effectiveness results. Probabilistic sensitivity analysis was undertaken to explore the impact of joint parameter uncertainty on the results. RESULTS: DTM-SCS was the most cost-effective option from a payer perspective. Compared with CMM alone, DTM-SCS was associated with an incremental cost-effectiveness ratio (ICER) of £6101 per QALY gained (incremental net benefit [INB] = £21,281). The INB for C-SCS compared with CMM was lower than for DTM-SCS, at £8551. For the comparison of DTM-SCS and C-SCS, an ICER of £897 per QALY gained was calculated, with a 99.5% probability of cost-effectiveness at a £20,000 per QALY threshold. CONCLUSIONS: Among patients with low back pain treated over a 15-year follow-up period, DTM-SCS and C-SCS are cost-effective compared with CMM, from both payer and societal perspectives. DTM-SCS is associated with a lower ICER than that of C-SCS. Wider uptake of DTM-SCS in the UK health care system is warranted to manage chronic low back pain.

Five-Year Longitudinal Follow-Up of Restorative Neurostimulation Shows Durability of Effectiveness in Patients With Refractory Chronic Low Back Pain Associated With Multifidus Muscle Dysfunction.

BACKGROUND: Adults with refractory, mechanical chronic low back pain associated with impaired neuromuscular control of the lumbar multifidus muscle have few treatment options that provide long-term clinical benefit. This study hypothesized that restorative neurostimulation, a rehabilitative treatment that activates the lumbar multifidus muscles to overcome underlying dysfunction, is safe and provides relevant and durable clinical benefit to patients with this specific etiology. MATERIALS AND METHODS: In this prospective five-year longitudinal follow-up of the ReActiv8-B pivotal trial, participants (N = 204) had activity-limiting, moderate-to-severe, refractory, mechanical chronic low back pain, a positive prone instability test result indicating impaired multifidus muscle control, and no indications for spine surgery. Low back pain intensity (10-cm visual analog scale [VAS]), disability (Oswestry Disability Index), and quality of life (EuroQol's "EQ-5D-5L" index) were compared with baseline and following the intent-to-treat principle, with a supporting mixed-effects model for repeated measures that accounted for missing data. RESULTS: At five years (n = 126), low back pain VAS had improved from 7.3 to 2.4 cm (-4.9; 95% CI, -5.3 to -4.5 cm; p < 0.0001), and 71.8% of participants had a reduction of ≥50%. The Oswestry Disability Index improved from 39.1 to 16.5 (-22.7; 95% CI, -25.4 to -20.8; p < 0.0001), and 61.1% of participants had reduction of ≥20 points. The EQ-5D-5L index improved from 0.585 to 0.807 (0.231; 95% CI, 0.195-0.267; p < 0.0001). Although the mixed-effects model attenuated completed-case results, conclusions and statistical significance were maintained. Of 52 subjects who were on opioids at baseline and had a five-year visit, 46% discontinued, and 23% decreased intake. The safety profile compared favorably with neurostimulator treatments for other types of back pain. No lead migrations were observed. CONCLUSION: Over a five-year period, restorative neurostimulation provided clinically substantial and durable benefits with a favorable safety profile in patients with refractory chronic low back pain associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354; registration date: October 15, 2016; principal investigator: Christopher Gilligan, MD, Brigham and Women's Hospital, Boston, MA, USA. The study was conducted in Australia (Broadmeadow, New South Wales; Noosa Heads, Queensland; Welland, South Australia; Clayton, Victoria), Belgium (Sint-Niklaas; Wilrijk), The Netherlands (Rotterdam), UK (Leeds, London, Middlesbrough), and USA (La Jolla, CA; Santa Monica, CA; Aurora, CO; Carmel, IN; Indianapolis, IN; Kansas City, KS; Boston, MA; Royal Oak, MI; Durham, NC; Winston-Salem, NC; Cleveland, OH; Providence, RI; Spartanburg, SC; Spokane, WA; Charleston, WV).

Long-Term Outcomes of Restorative Neurostimulation in Patients With Refractory Chronic Low Back Pain Secondary to Multifidus Dysfunction: Two-Year Results of the ReActiv8-B Pivotal Trial.

BACKGROUND: Impaired neuromuscular control and degeneration of the multifidus muscle have been linked to the development of refractory chronic low back pain (CLBP). An implantable restorative-neurostimulator system can override the underlying multifidus inhibition by eliciting episodic, isolated contractions. The ReActiv8-B randomized, active-sham-controlled trial provided effectiveness and safety evidence for this system, and all participants received therapeutic stimulation from four months onward. OBJECTIVE: This study aimed to evaluate the two-year effectiveness of this restorative neurostimulator in patients with disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. MATERIALS AND METHODS: Open-label follow-up of 204 participants implanted with a restorative neurostimulation system (ReActiv8, Mainstay Medical, Dublin, Ireland) was performed. Pain intensity (visual analog scale [VAS]), disability (Oswestry disability index [ODI]), quality-of-life (EQ-5D-5L), and opioid intake were assessed at baseline, six months, one year, and two years after activation. RESULTS: At two years (n = 156), the proportion of participants with ≥50% CLBP relief was 71%, and 65% reported CLBP resolution (VAS ≤ 2.5 cm); 61% had a reduction in ODI of ≥20 points, 76% had improvements of ≥50% in VAS and/or ≥20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 87% of participants had continued device use during the second year for a median of 43% of the maximum duration, and 60% (34 of 57) had voluntarily discontinued (39%) or reduced (21%) opioid intake. CONCLUSIONS: At two years, 76% of participants experienced substantial, clinically meaningful improvements in pain, disability, or both. These results provide evidence of long-term effectiveness and durability of restorative neurostimulation in patients with disabling CLBP, secondary to multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The study is registered on clinicaltrials.gov with identifier NCT02577354.

Three-Year Durability of Restorative Neurostimulation Effectiveness in Patients With Chronic Low Back Pain and Multifidus Muscle Dysfunction.

BACKGROUND: Restorative neurostimulation is a rehabilitative treatment for patients with refractory chronic low back pain (CLBP) associated with dysfunction of the lumbar multifidus muscle resulting in impaired neuromuscular control. The ReActiv8-B randomized, sham-controlled trial provided evidence of the effectiveness and safety of an implanted, restorative neurostimulator. The two-year analysis previously published in this journal demonstrated accrual of clinical benefits and long-term durability. OBJECTIVE: Evaluation of three-year effectiveness and safety in patients with refractory, disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. MATERIALS AND METHODS: Prospective, observational follow-up of the 204 implanted trial participants. Low back pain visual analog scale (VAS), Oswestry Disability Index (ODI), EuroQol quality of life survey, and opioid intake were assessed at baseline, six months, and one, two, and three years after activation. The mixed-effects model repeated measures approach was used to provide implicit imputations of missing data for continuous outcomes and multiple imputation for proportion estimates. RESULTS: Data were collected from 133 participants, and 16 patients missed their three-year follow-up because of coronavirus disease restrictions but remain available for future follow-up. A total of 62% of participants had a ≥ 70% VAS reduction, and 67% reported CLBP resolution (VAS ≤ 2.5cm); 63% had a reduction in ODI of ≥ 20 points; 83% had improvements of ≥ 50% in VAS and/or ≥ 20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 71% (36/51) participants on opioids at baseline had voluntarily discontinued (49%) or reduced (22%) opioid intake. The attenuation of effectiveness in the imputed (N = 204) analyses was relatively small and did not affect the statistical significance and clinical relevance of these results. The safety profile remains favorable, and no lead migrations have been observed to date. CONCLUSION: At three years, 83% of participants experienced clinically substantial improvements in pain, disability, or both. The results confirm the long-term effectiveness, durability, and safety of restorative neurostimulation in patients with disabling CLBP associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354.

The Use of Contrast Agents in Interventional Pain Procedures: A Multispecialty and Multisociety Practice Advisory on Nephrogenic Systemic Fibrosis, Gadolinium Deposition in the Brain, Encephalopathy After Unintentional Intrathecal Gadolinium Injection, and Hypersensitivity Reactions.

This Practice Advisory presents a comprehensive and evidence-based set of position statements and recommendations for the use of contrast media in interventional pain procedures. The advisory was established by an international panel of experts under the auspices of 11 multinational and multispecialty organizations based on a comprehensive review of the literature up to December 31, 2019. The advisory discusses the risks of using gadolinium-based contrast agents. These include nephrogenic systemic fibrosis, gadolinium brain deposition/retention, and encephalopathy and death after an unintentional intrathecal gadolinium injection. The advisory provides recommendations on the selection of a specific gadolinium-based contrast agent in patients with renal insufficiency, those who had multiple gadolinium-enhanced magnetic resonance imaging examinations, and in cases of paraspinal injections. Additionally, recommendations are made for patients who have a history of mild, moderate, or severe hypersensitivity reactions to contrast medium.

Analgesic Efficacy of "Burst" and Tonic (500 Hz) Spinal Cord Stimulation Patterns: A Randomized Placebo-Controlled Crossover Study.

OBJECTIVES: The aim of this study was to compare the efficacy in reducing pain intensity in adult subjects suffering from chronic back and leg pain of burst (BST) and tonic sub-threshold stimulation at 500 Hz (T500) vs. sham stimulation delivered by a spinal cord stimulation (SCS) device capable of automated postural adjustment of current intensity. MATERIALS AND METHODS: A multicentre randomized double-blind, three-period, three-treatment, crossover study was undertaken at two centers in the United Kingdom. Patients who had achieved stable pain relief with a conventional SCS capable of automated postural adjustment of current intensity were randomized to sequences of BST, T500, and sham SCS with treatment order balanced across the six possible sequences. A current leakage was programmed into the implantable pulse generator (IPG) in the sham period. The primary outcome was patient reported pain intensity using a visual analog scale (VAS). RESULTS: Nineteen patients were enrolled and randomized. The mean reduction in pain with T500 was statistically significantly greater than that observed with either sham (25%; 95% CI, 8%-38%; p = 0.008) or BST (28%; 95% CI, 13%-41%; p = 0.002). There were no statistically significant differences in pain VAS for BST versus Sham (5%; 95% CI, -13% to 27%; p = 0.59). Exploratory sub-group analyses by study site and sex were also conducted for the T500 vs. sham and BST versus sham comparisons. CONCLUSIONS: The findings suggest a superior outcome versus sham from T500 stimulation over BST stimulation and a practical equivalence between BST and sham in a group of subjects with leg and back pain habituated to tonic SCS and having achieved a stable status with stimulation.

Durability of the Therapeutic Effect of Restorative Neurostimulation for Refractory Chronic Low Back Pain.

OBJECTIVES: The purpose of the ongoing follow-up of ReActiv8-A clinical trial is to document the longitudinal benefits of episodic stimulation of the dorsal ramus medial branch and consequent contraction of the lumbar multifidus in patients with refractory mechanical chronic low back pain (CLBP). We report the four-year outcomes of this trial. MATERIALS AND METHODS: ReActiv8-A is a prospective, single-arm trial performed at nine sites in the United Kingdom, Belgium, and Australia. Eligible patients had disabling CLBP (low back pain Numeric Rating Scale [NRS] ≥6; Oswestry Disability Index [ODI] ≥25), no indications for spine surgery or spinal cord stimulation, and failed conventional management including at least physical therapy and medications for low back pain. Fourteen days postimplantation, stimulation parameters were programmed to elicit strong, smooth contractions of the multifidus, and participants were given instructions to activate the device for 30-min stimulation-sessions twice daily. Annual follow-up through four years included collection of NRS, ODI, and European Quality of Life Score on Five Dimensions (EQ-5D). Background on mechanisms, trial design, and one-year outcomes were previously described. RESULTS: At baseline (N = 53) (mean ± SD) age was 44 ± 10 years; duration of back pain was 14 ± 11 years, NRS was 6.8 ± 0.8, ODI 44.9 ± 10.1, and EQ-5D 0.434 ± 0.185. Mean improvements from baseline were statistically significant (p < 0.001) and clinically meaningful for all follow-ups. Patients completing year 4 follow-up, reported mean (±standard error of the mean) NRS: 3.2 ± 0.4, ODI: 23.0 ± 3.2, and EQ-5D: 0.721 ± 0.035. Moreover, 73% of participants had a clinically meaningful improvement of ≥2 points on NRS, 76% of ≥10 points on ODI, and 62.5% had a clinically meaningful improvement in both NRS and ODI and 97% were (very) satisfied with treatment. CONCLUSIONS: In participants with disabling intractable CLBP who receive long-term restorative neurostimulation, treatment satisfaction remains high and improvements in pain, disability, and quality-of-life are clinically meaningful and durable through four years.

To Trial or Not to Trial Before Spinal Cord Stimulation for Chronic Neuropathic Pain: The Patients' View From the TRIAL-STIM Randomized Controlled Trial.

Objectives Spinal cord stimulation (SCS) is an established treatment of chronic neuropathic pain. Although a temporary SCS screening trial is widely used to determine suitability for a permanent implant, its evidence base is limited. The recent TRIAL-STIM study (a randomized controlled trial at three centers in the United Kingdom) found no evidence that an SCS screening trial strategy provides superior patient outcomes as compared with a no trial approach. As part of the TRIAL-STIM study, we undertook a nested qualitative study to ascertain patients' preferences in relation to undergoing a screening trial or not. Materials and Methods We interviewed 31 patients sampled from all three centers and both study arms (screening trial/no trial) prior to SCS implantation, and 23 of these patients again following implantation (eight patients were lost to follow-up). Interviews were undertaken by telephone and audio-recorded, then transcripts were subject to thematic analysis. In addition, participants were asked to state their overall preference for a one-stage (no screening trial) versus two-stage (screening trial) implant procedure on a five-point Likert scale, before and after implantation. Results Emergent themes favoured the option for a one-stage SCS procedure. Themes identified include: saving time (off work, in hospital, attending appointments), avoiding the worry about having "loose wires" in the two-stage procedure, having only one period of recovery, and saving NHS resources. Participants' rated preferences show similar support for a one-stage procedure without a screening trial. Conclusions Our findings indicate an overwhelming preference among participants for a one-stage SCS procedure both before and after the implant, regardless of which procedure they had undergone. The qualitative study findings further support the TRIAL-STIM RCT results.

New Therapy for Refractory Chronic Mechanical Low Back Pain-Restorative Neurostimulation to Activate the Lumbar Multifidus: One Year Results of a Prospective Multicenter Clinical Trial.

OBJECTIVES: The purpose of the international multicenter prospective single arm clinical trial was to evaluate restorative neurostimulation eliciting episodic contraction of the lumbar multifidus for treatment of chronic mechanical low back pain (CMLBP) in patients who have failed conventional therapy and are not candidates for surgery or spinal cord stimulation (SCS). MATERIALS AND METHODS: Fifty-three subjects were implanted with a neurostimulator (ReActiv8, Mainstay Medical Limited, Dublin, Ireland). Leads were positioned bilaterally with electrodes close to the medial branch of the L2 dorsal ramus nerve. The primary outcome measure was low back pain evaluated on a 10-Point Numerical Rating Scale (NRS). Responders were defined as subjects with an improvement of at least the Minimal Clinically Important Difference (MCID) of ≥2-point in low back pain NRS without a clinically meaningful increase in LBP medications at 90 days. Secondary outcome measures included Oswestry Disability Index (ODI) and Quality of Life (QoL; EQ-5D). RESULTS: For 53 subjects with an average duration of CLBP of 14 years and average NRS of 7 and for whom no other therapies had provided satisfactory pain relief, the responder rate was 58%. The percentage of subjects at 90 days, six months, and one year with ≥MCID improvement in single day NRS was 63%, 61%, and 57%, respectively. Percentage of subjects with ≥MCID improvement in ODI was 52%, 57%, and 60% while those with ≥MCID improvement in EQ-5D was 88%, 82%, and 81%. There were no unanticipated adverse events (AEs) or serious AEs related to the device, procedure, or therapy. The initial surgical approach led to a risk of lead fracture, which was mitigated by a modification to the surgical approach. CONCLUSIONS: Electrical stimulation to elicit episodic lumbar multifidus contraction is a new treatment option for CMLBP. Results demonstrate clinically important, statistically significant, and lasting improvement in pain, disability, and QoL.

Comparison of the Effects of Intermittent Boluses to Simple Continuous Infusion on Patients' Global Perceived Effect in Intrathecal Therapy for Pain: A Randomized Double-Blind Crossover Study.

Objective: Intrathecal drug delivery (ITDD) is commonly used for intractable pain management. A paucity of good-quality studies in chronic noncancer patients and concerns over increased dosages have focused interest on different modes of administration. The aim of this international multicenter randomized double-blind crossover trial was to compare the efficacy of the same daily dose of drugs administered by intermittent boluses vs simple continuous infusion. Methods: Eligible patients implanted with a programmable ITDD device were randomized to receive two weeks of either intermittent boluses or a simple continuous flow in period 1, followed by a crossover to the alternative mode of administration. The primary outcome measure was the Patients' Global Impression of Change (PGIC) scale. Results: The mean proportion of positive responders (at least "minimally improved") was 38.4% in the continuous condition vs 37.3% in the bolus (difference in proportions = 1.1%, 95% confidence interval [CI] = -21.8-24.0%, P = 0.93). The mean PGIC in the continuous condition was 3.8 vs 3.9 in the bolus (mean difference = -0.1, -0.6-0.4, P = 0.72). Exploratory analyses revealed a tendency for the mean proportion of positive responders to be higher at low vs high flow rates for both bolus and continuous administrations. Two patients were withdrawn from the study due to adverse events during the bolus phase, both with symptoms of increased pain, and one patient with additional symptoms of numbness and urinary retention. Conclusion: The mean PGIC and proportion of positive responders was not substantially different after intermittent bolus vs continuous administration.

Chronic Low Back Pain: Restoration of Dynamic Stability.

OBJECTIVES: Electrical stimulation for multifidus muscle contraction is a novel approach for treating chronic low back pain (CLBP). A multicenter, open-label feasibility study investigated this modality in patients with continuing CLBP despite medical management and no prior back surgery and no known pathological cause of CLBP. METHODS: Twenty-six patients with continuing CLBP despite physical therapy and medication were implanted with commercially-available implantable pulse generators and leads positioned adjacent to the medial branch of the dorsal ramus as it crosses the L3 transverse process such that electrical stimulation resulted in contraction of the lumbar multifidus (LM) muscle. Patients self-administered stimulation twice daily for 20 min. Low back pain (VAS), Oswestry Disability Index (ODI) and Quality of Life (EQ-5D) scores were collected at three and five months and compared to baseline. Stimulation was withdrawn between months 4 and 5 to test durability of effect. RESULTS: At three months, 74% of patients met or exceeded the minimally important change (MIC) in VAS and 63% for disability. QoL improved in 84% of patients (N = 19) and none got worse. Five of the 11 patients on disability for CLBP (45%) resumed work by three months. Half the patients reported ≥50% VAS reduction by month 5. Twenty-one lead migration events occurred in 13 patients, of which 7 patients are included in the efficacy cohort. CONCLUSIONS: Episodic stimulation to induce LM contraction can reduce CLBP and disability, improve quality of life and enable return to work. A dedicated lead design to reduce risk of migration is required.

Spinal cord stimulation of the dorsal root ganglion for groin pain-a retrospective review.

BACKGROUND: Spinal cord stimulation (SCS) is a standard treatment option for chronic neuropathic pain. However, some anatomical pain distributions are known to be difficult to cover with traditional SCS-induced paresthesias and/or may also induce additional, unwanted stimulation. We present the results from a retrospective review of data from patients with groin pain of various etiologies treated using neuromodulation of the dorsal root ganglion (DRG). METHODS: Data from 29 patients with neuropathic groin pain were reviewed. Patients underwent trial therapy where specifically designed leads were implanted at the target DRGs between T12 and L4. Patients who had a successful trial (> 50% improvement) received the fully implantable neuromodulation system. Pain scores were captured on a visual analog scale (VAS) at baseline and at regular follow-up visits. RESULTS: Twenty-five patients (86.2%) received fully implantable neurostimulators, and the average follow-up period was 27.8 ± 4.3 (standard error of the mean, SEM) weeks. The average pain reduction was 71.4 ± 5.6%, and 82.6% (19/23) of patients experienced a > 50% reduction in their pain at the latest follow-up. Individual cases showed improvement with a variety of etiologies and pain distributions; a subanalysis of postherniorrhaphy cohort also showed significant improvement. CONCLUSIONS: Early findings suggest that neuromodulation of the DRG may be an effective treatment for chronic neuropathic pain conditions in the groin region. This technique offers a useful alternative for pain conditions that do not always respond optimally to traditional SCS therapy. Neuromodulation of the DRG provided excellent cross-dermatomal paresthesia coverage, even in cases with patients with discrete pain areas. The therapy can be specific, sustained, and independent of body position.

Durability of Evoked Compound Action Potential (ECAP)-Controlled, Closed-Loop Spinal Cord Stimulation (SCS) in a Real-World European Chronic Pain Population.

INTRODUCTION: Closed-loop spinal cord stimulation (CL-SCS) is a recently introduced system that records evoked compound action potentials (ECAPs) from the spinal cord elicited by each stimulation pulse and uses this information to automatically adjust the stimulation strength in real time, known as ECAP-controlled SCS. This innovative system compensates for fluctuations in the distance between the epidural leads and the spinal cord by maintaining the neural response (ECAP) at a predetermined target level. This data collection study was designed to assess the performance of the first CL-SCS system in a real-world setting under normal conditions of use in multiple European centers. The study analyzes and presents clinical outcomes and electrophysiological and device data and compares these findings with those reported in earlier pre-market studies of the same system. METHODS: This prospective, multicenter, observational study was conducted in 13 European centers and aimed to gather electrophysiological and device data. The study focused on the real-world application of this system in treating chronic pain affecting the trunk and/or limbs, adhering to standard conditions of use. In addition to collecting and analyzing basic demographic information, the study presents data from the inaugural patient cohort permanently implanted at multiple European centers. RESULTS: A significant decrease in pain intensity was observed for overall back or leg pain scores (verbal numerical rating score [VNRS]) between baseline (mean ± standard error of the mean [SEM]; n = 135; 8.2 ± 0.1), 3 months (n = 93; 2.3 ± 0.2), 6 months (n = 82; 2.5 ± 0.3), and 12 months (n = 76; 2.5 ± 0.3). Comparison of overall pain relief (%) to the AVALON and EVOKE studies showed no significant differences at 3 and 12 months between the real-world data release (RWE; 71.3%; 69.6%) and the AVALON (71.2%; 73.6%) and EVOKE (78.1%; 76.7%) studies. Further investigation was undertaken to objectively characterize the physiological parameters of SCS therapy in this cohort using the metrics of percent time above ECAP threshold (%), dose ratio, and dose accuracy (µV), according to previously described methods. Results showed that a median of 90% (40.7-99.2) of stimuli were above the ECAP threshold, with a dose ratio of 1.3 (1.1-1.4) and dose accuracy of 4.4 µV (0.0-7.1), based on data from 236, 230, and 254 patients, respectively. Thus, across all three metrics, the majority of patients had objective therapy metrics corresponding to the highest levels of pain relief in previously reported studies (usage over threshold > 80%, dose ratio > 1.2, and error < 10 µV). CONCLUSIONS: In conclusion, this study provides valuable insights into the real-world application of the ECAP-controlled CL-SCS system, highlighting its potential for maintaining effective pain relief and objective neurophysiological therapy metrics at levels seen in randomized control trials, and potential for quantifying patient burden associated with SCS system use via patient-device interaction metrics. CLINICAL TRIAL REGISTRATION: In the Netherlands, the study is duly registered on the International Clinical Trials Registry Platform (Trial NL7889). In Germany, the study is duly registered as NCT05272137 and in the United Kingdom as ISCRTN27710516 and has been reviewed by the ethics committee in both countries.

Bolus intrathecal injection of ziconotide (Prialt®) to evaluate the option of continuous administration via an implanted intrathecal drug delivery (ITDD) system: a pilot study.

OBJECTIVES: This study evaluated efficacy and safety of bolus doses of ziconotide (Prialt®, Eisai Limited, Hertfordshire, UK) to assess the option of continuous administration of this drug via an implanted intrathecal drug delivery system. MATERIALS AND METHODS: Twenty adults with severe chronic pain who were under consideration for intrathecal (IT) therapy were enrolled in this open label, nonrandomized, pilot study. Informed consent was obtained. Demographics, medical/pain history, pain scores, and concomitant medications were recorded. A physical examination was performed. Creatine kinase was measured. Initial visual analog scale (VAS), blood pressure, heart rate, and respiratory rate were recorded. All patients received an initial bolus dose of 2.5 mcg ziconotide; the dose in the subsequent visits was modified according to response. Subsequent doses were 2.5 mcg, 1.2 mcg, or 3.75 mcg as per protocol. A good response (≥30% reduction in baseline pain VAS) with no side-effects on two occasions was considered a successful trial. Data were analyzed using a generalized estimating equations model, with pain VAS as the outcome and time (seven time points; preinjection and one to six hours postinjection) as the predictor. RESULTS: Generalized estimating equations analysis of summary measures showed a mean reduction of pain VAS of approximately 25% at the group level; of 11 responders, seven underwent pump implantation procedure, two withdrew because of adverse effects, one refused an implant, and one could not have an implant (lack of funding from the Primary Care Trust). CONCLUSIONS: Our data demonstrated that mean VAS was reduced by approximately 25% at the group level after IT ziconotide bolus. Treatment efficacy did not vary with sex, center, age, or pain etiology. Ziconotide bolus was generally well tolerated. Larger studies are needed to determine if bolus dosing with ziconotide is a good predictor of response to continuous IT ziconotide via an intrathecal drug delivery system.

Cost-utility Analysis of Evoke Closed-loop Spinal Cord Stimulation for Chronic Back and Leg Pain.

OBJECTIVES: The effectiveness of Evoke closed-loop spinal cord stimulation (CL-SCS), a novel modality of neurostimulation, has been demonstrated in a randomized controlled trial (RCT). The objective of this cost-utility analysis was to develop a de novo economic model to estimate the cost-effectiveness of Evoke CL-SCS when compared with open-loop SCS (OL-SCS) for the management of chronic back and leg pain. METHODS: A decision tree followed by a Markov model was used to estimate the costs and outcomes of Evoke CL-SCS versus OL-SCS over a 15-year time horizon from the UK National Health Service perspective. A "high-responder" health state was included to reflect improved levels of SCS pain reduction recently reported. Results are expressed as incremental cost per quality-adjusted life year (QALY). Deterministic and probabilistic sensitivity analysis (PSA) was conducted to assess uncertainty in the model inputs. RESULTS: Evoke CL-SCS was estimated to be the dominant treatment strategy at ~5 years postimplant (ie, it generates more QALYs while cost saving compared with OL-SCS). Probabilistic sensitivity analysis showed that Evoke CL-SCS has a 92% likelihood of being cost-effective at a willingness to pay threshold of £20,000/QALY. Results were robust across a wide range of scenario and sensitivity analyses. DISCUSSION: The results indicate a strong economic case for the use of Evoke CL-SCS in the management of chronic back and leg pain with or without prior spinal surgery with dominance observed at ~5 years.

Does a Screening Trial for Spinal Cord Stimulation in Patients With Chronic Pain of Neuropathic Origin Have Clinical Utility (TRIAL-STIM)? 36-Month Results From a Randomized Controlled Trial.

BACKGROUND: Screening trials before full implantation of a spinal cord stimulation device are recommended by clinical guidelines and regulators, although there is limited evidence for their use. The TRIAL-STIM study showed that a screening trial strategy does not provide superior patient pain outcome at 6-month follow-up compared with not doing a screening trial and that it was not cost-effective. OBJECTIVE: To report the long-term follow-up results of the TRIAL-STIM study. METHODS: The primary outcome of this pragmatic randomized controlled trial was pain intensity as measured on a numerical rating scale (NRS) and secondary outcomes were the proportion of patients achieving at least 50% and 30% pain relief at 6 months, health-related quality of life, and complication rates. RESULTS: Thirty patients allocated to the "Trial Group" (TG) and 36 patients allocated to the "No Trial Group" (NTG) completed outcome assessment at 36-month follow-up. Although there was a reduction in NRS pain and improvements in utility scores from baseline to 36 months in both groups, there was no difference in the primary outcome of pain intensity NRS between TG and NTG (adjusted mean difference: -0.60, 95% CI: -1.83 to 0.63), EuroQol-5 Dimension utility values (adjusted mean difference: -0.02, 95% CI: -0.13 to 0.10), or proportion of pain responders (33% TG vs 31% NTG). No differences were observed between the groups for the likelihood of spinal cord stimulation device explant or reporting an adverse advent up to 36-month follow-up. CONCLUSION: The long-term results show no patient outcome benefit in undertaking an SCS screening trial.

A prospective long-term follow-up of dorsal root ganglion stimulation for the management of chronic intractable pain.

ABSTRACT: Initial clinical studies have shown that the stimulation of the dorsal root ganglion (DRG) can significantly reduce chronic intractable pain. However, clinical data on long-term results and complications of these systems are limited. The aim of this prospective study is to report on a single center long-term follow-up of DRG stimulation for intractable chronic pain. Participants were implanted with DRG stimulation devices between 2013 and 2015 with an observation period of 24 months. Patients were contacted again in 2020 for a final follow-up (ie, between 5 and 7 years postimplantation). Forty-two participants were recruited, of whom 32 received the fully implantable pulse generator (IPG). At the final follow-up, 50% (16/32) of participants were still using DRG stimulation. Two participants still had the original IPG and 14 had received a replacement IPG. Pain scores were significantly reduced at 24 months, mean difference 1.7 (95% confidence interval: 0.2-3.3, P = 0.03), and at the last follow-up, mean difference 2.1 (95% confidence interval: 0.3-4, P = 0.03). Significant improvements were observed for health-related quality of life. The findings were generally robust to imputation methods of missing data. Implantable pulse generators of 8 patients were explanted because of dissatisfaction with pain relief. In conclusion, DRG stimulation can provide effective pain relief and improved quality of life in patients suffering with neuropathic pain, although this study had a revision rate of 42% within the first 24 months, and 56% of IPGs that were replaced because of battery depletion had a shorter than expected battery life.

Screening trials of spinal cord stimulation for neuropathic pain in England-A budget impact analysis.

Screening trials of spinal cord stimulation (SCS) prior to full implantation of a device are recommended by expert guidelines and international regulators. The current study sought to estimate the budget impact of a screening trial of SCS and the costs or savings of discontinuing the use of a screening trial. A budget impact analysis was performed considering a study population that reflects the size and characteristics of a patient population with neuropathic pain in England eligible for SCS. The perspective adopted was that of the NHS with a 5-year time horizon. The base case analysis indicate that a no screening trial strategy would result in cost-savings to the NHS England of £400,000-£500,000 per year. Sensitivity analyses were conducted to evaluate different scenarios. If ≥5% of the eligible neuropathic pain population received a SCS device, cost-savings would be >£2.5 million/year. In contrast, at the lowest assumed cost of a screening trial (£1,950/patient), a screening trial prior to SCS implantation would be cost-saving. The proportion of patients having an unsuccessful screening trial would have to be ≥14.4% for current practice of a screening trial to be cost-saving. The findings from this budget impact analysis support the results of a recent UK multicenter randomized controlled trial (TRIAL-STIM) of a policy for the discontinuation of compulsory SCS screening trials, namely that such a policy would result in considerable cost-savings to healthcare systems.

Prospective analysis of the trial period for spinal cord stimulation treatment for chronic pain.

OBJECTIVE: To determine patient preferences regarding the duration of trial period. MATERIALS AND METHODS: Forty patients were given a trial of spinal cord stimulation. They were questioned daily if they would like to proceed to a permanent implant. Three consecutive affirmative answers implied a successful trial; three negative replies implied a failed trial. Patients rated daily the pain from the surgery, original pain, satisfaction with the stimulator, and the duration of the use of the stimulator. RESULTS: The trial duration varied from 3 to 15 days. Patients with a failed trial took longer to make a decision and also experienced prolonged surgical pain. The majority of patients with a successful trial experienced more than 50% pain reduction. The rate of infection was 7.5%, which has reduced to 2.8% after changing the dressing protocol. CONCLUSIONS: In this study, all patients could make a decision in 15 days, with successful trials requiring a shorter duration. The conversion rate was similar to rates in literature despite patients making a decision without physician input.

The impact of the COVID-19 pandemic on patients awaiting spinal cord stimulation surgery in the United Kingdom: a multi-centre patient survey.

INTRODUCTION: Spinal cord stimulation (SCS) is a recommended treatment for chronic refractory neuropathic pain. During the COVID-19 pandemic, elective procedures have been postponed indefinitely both to provide capacity to deal with the emergency caseload and to avoid exposure of elective patients to COVID-19. This survey aimed to explore the effect of the pandemic on chronic pain in this group and the views of patients towards undergoing SCS treatment when routine services should resume. METHODS: This was a prospective, multi-centre telephone patient survey that analysed data from 330 patients with chronic pain who were on an SCS waiting list. Questions focussed on severity of pain, effect on mental health, medication consumption and reliance on support networks during the COVID-19 pandemic. Views towards undergoing SCS therapy were also ascertained. Counts and percentages were generated, and chi-square tests of independence explored the impact of COVID-19 risk (very high, high, low) on survey responses. RESULTS: Pain, mental health and patient's ability to self-manage pain deteriorated in around 47%, 50% and 38% of patients, respectively. Some patients reported increases in pain medication consumption (37%) and reliance on support network (41%). Patients showed a willingness to attend for COVID-19 testing (92%), self-isolate prior to SCS (94%) and undergo the procedure as soon as possible (76%). CONCLUSION: Our findings suggest that even during the COVID-19 pandemic, there remains a strong clinical need for patients with chronic pain identified as likely SCS responders to be treated quickly. The current prioritisation of new SCS at category 4 (delayed more than 3 months) is challenged judging by this national survey. These patients are awaiting SCS surgery to relieve severe intractable neuropathic pain. A priority at category 3 (delayed up to 3 months) or in some selected cases, at category 2 are the appropriate priority categories.